Novel isosteres and bioisosteres of natural styryl lactones: design,synthesis and antiproliferative activity

Abstract

<p>U&nbsp; radu&nbsp; su&nbsp; ostvarene&nbsp; vi&scaron;efazne&nbsp; sinteze&nbsp; većeg&nbsp; broja&nbsp; analoga&nbsp; prirodnih&nbsp; stiril-laktona&nbsp; (+)-goniofufurona&nbsp; i&nbsp; 7-epi-(+)-goniofufurona&nbsp; polazeći&nbsp; iz&nbsp; D-glukoze.<br />Ispitana&nbsp; je&nbsp; in&nbsp; vitro&nbsp; citotoksičnost&nbsp; sintetizovanih&nbsp; analoga&nbsp; prema&nbsp; devet<br />malignih&nbsp; i&nbsp; jednoj&nbsp; zdravoj&nbsp; ćelijskoj&nbsp; liniji.&nbsp; Uspostavljeni&nbsp; su&nbsp; korelacioni&nbsp; odnosi<br />izmedju&nbsp; strukture&nbsp; i&nbsp; antiproliferati vne&nbsp; aktivnosti&nbsp; sintetizovanih&nbsp; proizvoda, pored&nbsp; toga&nbsp; uradjeni&nbsp; su&nbsp; i&nbsp; dodatni&nbsp; biolo&scaron;ki&nbsp; testovi&nbsp; koji&nbsp; se&nbsp; odnose&nbsp; na dokazivanje&nbsp; mehanizma&nbsp; citotoksičnog&nbsp; dejstva&nbsp; pomenutih&nbsp; stiril-laktona&nbsp; i analoga.</p>

<p>Multistep&nbsp; synthesis&nbsp; of&nbsp;&nbsp; a&nbsp; number&nbsp; of&nbsp; natural&nbsp; styryl&nbsp; lactones&nbsp;goniofufurone&nbsp; and&nbsp; 7-epi-goniofufurone&nbsp; analogues&nbsp; was&nbsp; achieved&nbsp;starting&nbsp; f rom&nbsp; D-glucose.&nbsp; In&nbsp; vitro&nbsp; cytotoxicity&nbsp; of&nbsp; newly&nbsp; synthetized analogues&nbsp; against&nbsp; nine&nbsp; human&nbsp; tumour&nbsp; cell&nbsp; lines&nbsp; and&nbsp; against&nbsp; a single normal cell line was evaluated. Structure-activity relationships were&nbsp; established&nbsp; for&nbsp; both&nbsp; natural&nbsp; products&nbsp; and&nbsp; analogues.&nbsp; Some additional&nbsp; biological&nbsp; tests&nbsp; related&nbsp; to&nbsp; the&nbsp; cell mechanisms&nbsp; underlying the&nbsp; cytotoxicity&nbsp; of&nbsp;&nbsp; the&nbsp; mentioned&nbsp; styryl&nbsp; lactones&nbsp; and&nbsp; analogues, were also carried out.</p>